PXD012941

PXD012941 is an original dataset announced via ProteomeXchange.

Title	Lysine-specific demethylase 2A enhances binding of various nuclear factors to CpG-rich genomic DNAs by action of its CXXC-PHD domain
Description	The lysine-specific demethylase 2A gene (KDM2A) is ubiquitously expressed and its transcripts consist of several alternatively spliced forms, including KDM2A and the shorter form N782 that lacks the 3’ end encoding F-box and LRR. KDM2A binds to numerous CpG-rich genomic loci and regulates various cellular activities; however, the mechanism of the pleiotropic function is unknown. Here, we identify the mechanism of KDM2A played by its CXXC-PHD domain. KDM2A is necessary for a rapid proliferation of post-natal keratinocytes while its 3’ end eclipses the stimulatory effect. EGFP-N782 binds to chromatin together with the XRCC5/6 complex, and the CXXC-PHD domain regulates the CpG-rich IGFBPL1 promoter. In vitro, CXXC-PHD enhances binding of nuclear extract ORC3 to the CpG-rich promoter, but not to the AT-rich DIP2B promoter to which ORC3 binds constitutively. Furthermore, CXXC-PHD recruits 94 nuclear factors involved in replication, ribosome synthesis, and mitosis, including POLR1A to the IGFBPL1 promoter. This recruitment is unprecedented; however, the result suggests that these nuclear factors bind to their cognate loci, as substantiated by the result that CXXC-PHD recruits POLR1A to the rDNA promoter. We propose that CXXC-PHD promotes permissiveness for nuclear factors to interact, but involvement of the XRCC5/6 complex in the recruitment is undetermined.
HostingRepository	PRIDE
AnnounceDate	2019-06-28
AnnouncementXML	Submission_2019-06-28_05:08:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidoethyl-L-cysteine; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-04 01:41:58	ID requested
⏵ 1	2019-06-28 05:08:50	announced

Iuchi S, Paulo JA, Lysine-specific demethylase 2A enhances binding of various nuclear factors to CpG-rich genomic DNAs by action of its CXXC-PHD domain. Sci Rep, 9(1):5496(2019) [pubmed]

curator keyword: Biological

submitter keyword: GeLC-MS/MS, Tandem mass tag

Joao A. Paulo
contact affiliation	Joao A. Paulo, Department of Cell Biology, Harvard Medical School, Boston, MA, USA
contact email	joao_paulo@post.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012941
     1. Label: PRIDE project
     2. Name: Lysine-specific demethylase 2A enhances binding of various nuclear factors to CpG-rich genomic DNAs by action of its CXXC-PHD domain